Gene V protein of bacteriophage f1 binds ssDNA or ssRNA with high affinity and cooperativity, and prevents replication of viral ssDNA into parental DNA. The gene V protein coats ssDNA forming an ordered left-handed superhelical array. The gene V protein has provided an excellent model for studying the effects of amino acid substitution on protein stability and function because of its relative small size and the large number of mutants available. We have recently crystallized a systematic series of hydrophobic core mutations in gene V protein for X-ray crystallographic analysis.